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TOPIC NUMBER 0
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TOPIC NUMBER 1
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Firm Name: Pharmaview Inc dba Far Hills Pharmacy
Record Date: 2019-11-14 00:00:00
Topic Probability: 0.9955310821533203
Observation:
('ITY, STATE AND ZIP CODE 3edminster, NJ 07921-2605 TYPE OF ESTABLISHMENT '
'INSPECTED Producer of Non-Sterile Drugs HIS DOCUMENT LISTS OBSERVATIONS '
'MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. '
'THEY ARE INSPECTIONAL IBSERVATIONS; AND DO NOT REPRESENT A FINAL AGENCY '
'DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING '
'AN IBSERVATION, OR HAVE IMPLEMENTED, OR PLAN TO IMPLEMENT CORRECTIVE ACTION '
'IN RESPONSE TO AN OBSERVATION, YOU MAY DISCUSS THE IBJECTION OR ACTION WITH '
'THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OR SUBMIT THIS INFORMATION '
'TO FDA AT THE ADDRESS ABOVE. IF ‘OU HAVE ANY QUESTIONS, PLEASE CONTACT FDA '
'AT THE PHONE NUMBER AND ADDRESS ABOVE. JURING AN INSPECTION OF YOUR FIRM '
'(1) (WE) '
'OBSERVED: '
'JBSERVATION | jazardous drugs were compounded without providing adequate '
'containment or cleaning of multi-use equipment O prevent '
'cross-contamination. . specifically, Juring the compounding operations '
'observed on 10/29/2019 of Estradiol + Testosterone 0.01% + 0.01% in 30 g, ve '
'notice that once the Estradiol was collected and weighed it was placed on '
'the working surface next to other aw materials without proper containment. '
'Your firm compounds the following hazardous drugs: Progesterone Micro USP '
'Capsules, Biestrogen + Testosterone in Phyto Base, Estradiol + Estriol + '
'Progesterone in HRT, and {stradiol + Progesterone Capsules. In addition, '
'there is a lack of cleaning with an adequate deactivating agent to nsure '
'that residue of hazardous drugs is absent from multi-use equipment such '
'as(b) (4) (b) (4) b) (4) and plastic syringe. IBSERVATION 2 '
'Non-Pharmaceutical grade components are use in the formulation of '
'non-sterile drug products. specifically, a. Non-pharmaceutical grade '
'component (b) (4) was observed on the shelf. This component was used in the '
'formulation of the following non-sterile drug products: alam Iat 193N071D) '
'nraduced an Inlw 30 9N10 405 Main St TYPE OF ESTABLISHMENT INSPECTED ~ '
'Riectrnaen + Tectnactarnne in Phuta Race 19 +1 9 harmaview Inc (DOB: Far '
'Hills Pharmacy) TY, STATE AND ZIP CODE edminster, NJ 07921-2605 Producer '
'of Non-Sterile Drugs - Testosterone in Phyto Base 4mg/ml, lot 190306D, '
'produced on June 03, 2019. b. There is no assurance that the (b) (4) used '
'as a component in the formulation of non-sterile drug products, complies as '
'pharmaceutical grade (b) (4) . Examples of products produced with this (6) '
'(4) as a component are: - Pyridoxine Suspension 50mg/ml, lot 193007F, '
'produced on July 30, 2019 - Minoxidil 5% Scalp Solution 30ml, lot 192708G, '
'produced on August 27, 2019. - Aminophyllin in HRT 10% 100mg/g, lot 192709A, '
'produced on September 27, 2019. ')
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Firm Name: Professional Pharmacy Services Inc dba Good Day Pharmacy
Record Date: 2019-06-17 00:00:00
Topic Probability: 0.9952446222305298
Observation:
('You produced highly potent drugs without providing adequate containment, '
'segregation, cleaning of work surfaces and cleaning of utensils to prevent '
'cross-contamination. Specifically, Equipment, work surfaces, and utensils '
'are used for the production of hormonal products as well as non-hormonal '
'products. Inadequate cross-contamination precautions are established to '
'protect drug products produced on these shared surfaces at the Good Day '
'Longmont location as well as the Good Day Fort Collins location. You have '
'failed to demonstrate that the use of the dish washer and manual cleaning '
'operations (soap and water) are adequate to mitigate cross-contamination of '
'products made on site. Non-dedicated equipment, utensils, and work surfaces '
'include the(b) (4) ‘hood, compounding counter adjacent to the hood, glass '
'stirrers, metal spatulas, glass mortar and pestle, mesh sieves, (b) (4) '
'capsule machines, unguator and mixing blades, ointment mill, troche mold, '
'stir bars, and beakers. a. On 6/4/2019 you made the following hormone '
'containing prescription products and non-hormone containing prescription '
'products with mixed use equipment, utensils, and workstations: Testosterone '
'10mg Mini Troche Rx (b) (6) roches Progesterone 100mg IR Capsule Rx (b) '
'(6).) -apsules . BIEST (50:50) 0.1mg/gm(b)\\ (4) 01.me/em cream Rx (6)i(6).) '
'@ Progesterone 75mg SR #1 75mg Capsule Rx (6)/(6). © @-apsules Enrof '
'20mg/Prednisolone eae Oral Suspension Rx (b) (6). (b) (4) Prazosin 0.5mg '
'Capsule Rx (b) (6), b) (4) Ranitidine 30mg/mL Glycerin Oral Suspension Rx '
'(6)\\(6) (B) (4) Clonidine 0.1mg/mL Oral Suspension Rx(b) (6) (b) (4) b. '
'On 6/7/2019 you made the following hormone containing products and '
'non-hormone containing products with mixed use equipment, utensils, and '
'workstations (b) (4) (B) (4) hood and compounding counter adjacent to the '
'hood): Estradiol Smg/gm Cream Rx (b) (6) (b) (4) Estradiol 15mg/gm Cream '
'Rx(b) (6). (®) (4) ag ES bg Pregnenolone 65mg/ Progesterone 200mg/ '
'Testosterone 0.65mg Sugar Free Troche Rx (6) (6) © @)roches Testosterone '
'16% (160mg/gm) Cream Rx (b) (6) () (4) Gabapentin 50mg #3 Capsule Rx (6) '
'(6). capsules _ Omeprazole 2mg/ml Oral Suspension Rx (6) (6), (D) (4) ')
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Firm Name: Blount Discount Pharmacy, Inc.
Record Date: 2020-02-13 00:00:00
Topic Probability: 0.9939913749694824
Observation:
('Y, STATE AND ZIP CODE coa. TN 37701 TYPE OF ESTABLISHMENT INSPECTED '
'Non-sterile Drug Product Producer S DOCUMENT LISTS OBSERVATIONS MADE BY '
'THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE '
'INSPECTIONAL SERVATIONS; AND DO NOT REPRESENT A FINAL AGENCY DETERMINATION '
'REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING AN SERVATION, '
'OR HAVE IMPLEMENTED, OR PLAN TO MPLEMENT CORRECTIVE ACTION IN RESPONSE TO AN '
'OBSERVATION, YOU MAY DISCUSS THE JECTION OR ACTION WITH THE FDA '
'REPRESENTATIVE(S) DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT '
'THE ADDRESS ABOVE. IF U HAVE ANY QUESTIONS, PLEASE CONTACT FDA AT THE PHONE '
'NUMBER AND ADDRESS ABOVE. RING AN INSPECTION OF YOUR FIRM (I) (WE) '
'OBSERVED: bservation #1 wzardous and highly potent drugs are produced '
'without providing adequate cleaning of work surfaces, utensils, uipment '
'and/or personnel to prevent cross-contamination. cifically, I observed '
'built-up residue on the scale, stained and nicked spatulas, scratched and '
'cloudy glassware ed to produce non-sterile drug products. You use these same '
'utensils and equipment to manufacture hazardous ugs and non-hazardous types '
'of drugs including but not limited to hormone, Fluorouracil, and opioid '
'products. bservation #2 yents used for cleaning the laminar flow hood and '
'other equipment between products do not include a activating agent (e.g. '
'oxidizing agent) to prevent cross-contamination. cifically, the cleaning '
'agents I observed used between batches for equipment and the hood were | | '
'and dish soap only. bservation #3 n-pharmaceutical grade components are '
'used in the formulation of non-sterile drug products. ecifically, you '
'use Sodium Hyaluronate, a as components in hormone creams, cough up and '
'suspensions. You do not have adequate documentation to demonstrate these '
'components meet suitability ‘use in non-sterile drug products. ')
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TOPIC NUMBER 2
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Firm Name: ImClone Systems, L.L .C.
Record Date: 2019-11-26 00:00:00
Topic Probability: 0.9971312284469604
Observation:
('Appropriate controls are not exercised over computers or related production '
'systems. Specifically, electronic data obtained from manufacturing process '
'or related equipment are not appropriately controlled. For example, A. We '
'observed from the audit trails of the(b) (4) units that electronic files '
'identified as Calibration Study, Qualification Study and Verification Study '
'have been deleted. These §) (4) (b) (4) | , units are used for the equipment '
'qualifications, involving (b) (4) — i processes. The deleted incidents and '
'related audit trail were not reviewed by the quality unit. For example, the '
'following are some of the actions observed in the audit trai] obtained from '
'the(b) (4) ) units. 3 |-Jan-2018 Qualification Study : (b) ) (4) d '
'‘deleted by at 15:57:48 User ID (6) (6)”. User Name: (b) 6) 01-Feb-2018 '
'Qualification Study :(b) (4) deleted by at 09:22:17 User ID : (b) (6). User '
'Name: (6))(4) Branchburg, NJ 08876-3904 Biological Drug Substance '
'Manufacturer 05-Feb-2018 | Verification Study : (B)(4) =” deleted by '
'at 14:15:14 User ID : (6) (6). User Name: (6)(6) 05-Feb-2018 Calibration '
'Study :(b) (4) _” deleted by at 14:17:03 User ID : (6){4)". User Name: '
'(b)(@) 05-Feb-2018 Calibration Study : “(b) (4) deleted by at 14:17:19 User '
'ID : (b)(4)”. User Name: (b) (4) 05-Feb-2018 Verification Study : (6) 4) '
'deleted at 14:17:38 by User ID: ont User Name (b) (4) 05-Feb-2018 | '
'Verification Study : Jy (D)(4) deleted by at 14:18:05 User ID : “(by {4y. '
'User (b) (4) 05-Feb-2018 Qualification Study : “(b) (4) i at 14:20:22 '
'deleted by User ID : (6)(6)”. User Name: (b) (6) 22-Feb-2018 Qualification '
'Study : (b) (4) _ at 07:06:39 deleted by User ID : (6) (6). User Name: (b) '
'(6) 23-Mar-2018 | Qualification Study : (B)4)NN deleted at 09:01:04 by User '
'ID : (B) (6) User Name: (6) (6) 13-Apr-2018 Qualification Study : “(B)(4) '
'at 09:57:49 deleted by User ID : (6)(6)". User Name: (b) (6) '
'Branchburg, NJ 08876-3904 | Biological Drug Substance '
'Manufacturer 16-Aug-2018 | Qualification Study :{b) (4) '
'—_—_ deleted by at 13:49:53 User ID : (b) (6). User Name: (6) (6) '
"05-Feb-2018 Verification Study: (6) (4) ' deleted by at 14:15:14 User ID: "
'(6) ©)”. User Name (b) (6) 05-Feb-2018 Calibration Study: (6) (6) _ deleted '
'by at 14:17:03 User ID: (B)(6). User Name (b) (6) 05-Feb-2018 Calibration '
'Study: (6) (4) deleted by at 14:17:19 User ID: (6)(6)”. User Name: (b) (6) '
'05-Feb-2018 | Verification Study: (b) (4) deleted by at 14:17:38 User ID: '
'(6) (6)) User Name: (6) @) 05-Feb-2018 Verification Study: (6) (4) deleted '
'by at 14:18:05 User ID: (6) (6). User Name: ()(6) 05-Feb-2018 Qualification '
'Study: (6)(4)_ at 14:19:51 deleted by User ID: (6)(6) User Name: (b) (6) '
'13-Apr-2018 Qualification Study: “(b) (4) at 09:57:49 deleted by User ID: '
'(6)(6). User Name: * Full name withheld, and only '
'initials shown Branchburg, NJ 08876-3904 Biological Drug Substance '
'Manufacturer B. Review of the (b) (4) _unit’s (Serial No(b) (4) _) audit '
'trail also indicated users had logged into the system on multiple occasions '
'to do Audit Trail operations followed by adjusting the system clock. For '
'example, the following table shows three sequential actions recorded in the '
'audit trail: : 38- Sep-2018 User Td: OG) TPE in to ane, at 10:50:13 '
'28-Sep-2018 User Id : (6) (6) . User Name: "* logged i in at 11:03:47 to do '
'“AuditTrail” operation in (b) (4 ee screen 28-Sep-2018 (6) (4) Clock '
'adjusted from at 10:48:59 28/09/2018 11:03:47 to 28/09/2018 10:49:00 by '
'User Id : (6) (6), User Name:(6) ©) * Full name withheld, '
'and only initials shown Similar actions were observed in (b) (4) > units, '
'(6) (4) sand (B) (4) as well. The firm’s quality unit did not review the '
'audit trails from these (b) (4) = =————suunits. Operators were assigned '
'administrative privileges. In addition, the firm does not have sufficient '
'controls ta prevent the deletion of electronic data stored in these systems, '
'which is not backed-up on a periodic basis. C. We observed that test runs '
'have been aborted from(b) (4) — _ Test Instruments and the aborted tests '
'were not logged in the user logs, documented or reviewed. For example, '
'review of the run history on the(b) (4) Test Instruments (ID: (6)(4) ) '
'indicated an error message “Test aborted by the operator” on multiple '
'occasions. However, these events were not Branchburg, NJ 08876-3904 '
'Biological Drug Substance Manufacturer documented in the user logs and '
'reviewed by the quality unit. We were unable to ascertain why the operators '
'had aborted the runs. These (6) (4) | Test Instruments are used to conduct '
'(b) (4)) and (b) (4) _ testing of (6) (4) , that are used in the '
'manufacturing processes of biological drug substances such as Cetuximab, '
'Ramucirumab, Necitumumab and Galcanezumab, which are utilized in the '
'production of drug products that are distributed in the U.S. '
'market. ')
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Firm Name: Edge Pharma, LLC
Record Date: 2020-03-30 00:00:00
Topic Probability: 0.9946402907371521
Observation:
('Routine calibration and checking of automatic, mechanical and electronic '
'equipment is not performed according to a written program designed to assure '
'proper performance. Specifically, the firm has not adequately qualified all '
'equipment as capable of performing its intended functions or operations '
'before first use and your firm does not perform routine maintenance for all '
'equipment. For example: A. Your firm has not adequately qualified all '
'critical equipment used to produce, test, and store sterile drug products to '
'include: (B) (4) . temperature control chambers (incubators). and '
'refrigerators. For example, the firm’s initial qualification of refrigerator '
'Model (b) (4) (ID# NS-FRIG- 022) was inadequate. The firm failed to conduct '
'an installation qualification (IQ) or operational qualification (OQ) (i.e. '
'empty chamber mapping). The firm’s performance qualification (PQ) only '
'consisted of an(b) (4) chamber mapping. The PQ failed to include open door '
'and recovery testing, power-loss simulation or alarms testing. The '
'aforementioned refrigeration unit is located within the QC Laboratory and is '
'utilized for the storage of samples awaiting QC analysis and for the storage '
'of stability samples. B. The firm uses a(b) (4) water system to generate '
'water which is subsequently (b) (4) into plastic buckets and used for '
'dilution of disinfecting agents used in ISO-7 and ISO-8 classified spaces; '
'however, there is no assurance the water used for the dilution of '
'disinfecting agents and used for cleaning of ceilings, walls, and floors is '
'appropriate for use. For example: the fe (4) (b) (4) water system has not '
'been qualified and the firm does not perform(b) (4 of (b) (4) (6) (4)used on '
'the water system. In addition, on 3/6/20, the(b) (4) (Lot (b) (4)) used '
'every (b) (4) for sanitizing and disinfecting the system were observed '
'expired (expiry date of 11/05/2018), and the (Bb) (4) _ located on the water '
'hold tank was observed as expired. Further, plastic buckets used to transpor '
'(fb) (4) water to classified spaces are(b) (4) with non- sterile™™ and '
'filled in a non-classified environment. ')
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Firm Name: Edge Pharma, LLC
Record Date: 2020-03-30 00:00:00
Topic Probability: 0.9946087598800659
Observation:
('Procedures designed to prevent microbiological contamination of drug '
'products purporting to be sterile are not established and followed. '
'Specifically, A. The firm failed to follow standard operating procedure '
'(SOP), S-CMP-012, Aseptic Technique, which states "cleanroom technicians '
'must move slowly, deliberately and avoid excess or unnecessary movements '
'while working within classified areas". For example, on 3/4/20 through '
'3/6/20, firm personnel were observed to qove rapidly within the ISO-7 Clean '
'Room 202, immediately adjacent to the open ISO-5_ LFHs during sterile '
'compounding. In addition, (SOP), S-CMP-012, Aseptic Technique, fails to '
'address personnel controls to prevent unnecessary activities that could '
'increase the potential for introducing contaminants into ISO-5 environments. '
'For example, on 3/9/20, firm personnel operating within ISO- | LFHs were '
'observed to place their forearms and elbows on the deck of the ISO-5|_ '
'LFHs. B. The firm’s production & operations staff failed to follow '
'procedure, P#.2.1.1 — Deproygenating Reusable Devices and Glassware, to '
'store depyrogenated, aluminum sealed glassware and reusable devices in an '
'ISO class 8, or better, environment. During the current inspection, aluminum '
'sealed glassware to include 20L beakers used during sterile drug production '
'was found stored on a cart in a non-classified environment. C. The firm has '
'not performed an assessment to determine if non-sterile hand sanitizer is '
'adequate to be used during sterile gowning. For example, the firm utilizes '
'non-sterile (b) (4) (b) (4) ) on non-sterile gloved hands during the gowning '
'process to enter the ISO-7 Clean Room 202 prior to the final step of putting '
'on sterile gloves. During the inspection, employees were observed touching '
'their sterile garments after utilizing the non-sterile hand sanitizer. '
'Deficiencies regarding prevention of microbiological contamination of drug '
'products were also noted during the 2014 and 2018 FDA inspections ')
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TOPIC NUMBER 3
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Firm Name: Hawaii Health Systems Corporation dba Kona Community Hospital Pharmacy
Record Date: 2019-12-13 00:00:00
Topic Probability: 0.9967184066772461
Observation:
('Your facility design allowed the influx of poor quality air into a higher '
'classified area. Specifically, the air balance between rooms is not '
'controlled to ensure cascading flow of air between areas of lesser '
'classifications. For example: COLT (°C) | area does not seal completely '
'when the doors on either side of (b) (4) j The ISO 7 Hazardous Drug Room is '
'maintained at a negative pressure relative to adjacent spaces, allowing air '
'from the unclassified area to continuously enter the room. The differential '
'pressure between the ISO 7 Hazardous Drug Room and the unclassified office '
'area is not monitored. Additionally, during the transfer of finished sterile '
'hazardous drugs, we observed (b) (4) open at the same time. The ISO 7 '
'Hazardous Drug Room contains the ISO 5 Biosafety Cabinet, which is used in '
'the production of sterile hazardous drug products, including but not limited '
'to Leucovorin, Oxaliplatin, Fluorouracil, Gemcitabine, and Cisplatin. b.) '
'The air pressure differential between the ISO 8 Ante Room and the '
'unclassified office area has been below the specified range of (b) (4) '
'inches water column (” w.c.) on 39 of the 44 days between 10/09/19 and '
'12/05/19 for which data was recorded. Of the 39 instances, the pressure '
'differential was measured as negative once on 11/13/19 at -0.003” w.c. '
'allowing air from the ISO 8 Ante Room into the ISO 7 Non-Hazardous Drug '
'Room. The ISO 8 Ante Room is used by operators performing production '
'operations to don sterile garbing materials prior to entering one of the ISO '
'7 areas and the Ante Room is also used for storage of materials used for '
'production operations. c.) The air pressure differential between the ISO 7 '
'Non-Hazardous Drug Room and the ISO 8 Ante Room has been below and above the '
'specified range of (b) (4) _” w.c. on 8 of the 44 days between 10/09/19 and '
'12/05/19 for which data was recorded. The ISO 7 Non-Hazardous Drug Room '
'contains the ISO 5 Laminar Airflow Hood, which is used in the production of '
'sterile non-hazardous drug products, including but not limited to '
'Vancomycin, Phenylephrine, Penicillin, Ceftriaxone, and Fentanyl. d.) The '
'air pressure differential between the ISO 7 Hazardous Drug Room and the ISO '
'7 Non-Hazardous Drug Room has been below the specified range of negative (b) '
'(4) ” w.c. on 38 of the 44 days between 10/09/19 and 12/05/19 for which data '
'was recorded. e.) During the cleanroom certification performed on 12/11/18, '
'the following air pressure differentials were out of specification: between '
'the ISO 8 Ante Room and unclassified office area was measured at 0.138” w.c. '
'using a calibrated instrument while the firm’s wall gauge reading was 0.108” '
'w.c., and between the ISO 7 Non- Hazardous Drug Room and ISO 8 Ante Room was '
'measured at 0.00556” w.c. using a calibrated instrument while the firm’s '
'wall gauge reading was 0.044. The subsequent and most recent certification '
'performed on 06/05/19 also had air pressure differentials out of '
'specification: between the ISO 8 Ante Room and unclassified office area was '
'measured at 0.145” w.c. (-0.132” w.c. wall gauge), between the ISO 7 Non- '
'Hazardous Room and the ISO 8 Ante Room was measured at 0.00573” w.c. (0.01” '
'w.c. wall gauge), and between the ISO 7 Hazardous Drug Room and ISO 7 '
'Non-Hazardous Drug Room was measured at -0.0719” w.c. (-0.084” w.c.). The '
'wall gauges used for daily readings have never been calibrated. ')
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Firm Name: Roger Williams Medical Center
Record Date: 2019-08-14 00:00:00
Topic Probability: 0.9959396719932556
Observation:
('Your facility design allowed the influx of poor quality air into a higher '
'classified area. Specifically, A. There is an|(®))/@) the unclassified '
'pharmacy area and the ISO 7 classified Clean Room |\\*)) <5) the '
'unclassified pharmacy area and the ISO 7 classified Chemo Room. Components '
'used in production are|(®)) G5 (b) (4) were observed to be cluttered with '
'papers, supplies and equipment. You do not have information or data to '
'provide assurance that the unclassified air from the pharmacy area is not '
'entering the ISO 7 classified Clean Room and Chemo Room though the|(s))@5 '
'during production. B. You do not monitor the pressure differential between '
'the ISO 7 Ante Room and the ISO 7 Chemo Room. On 07/22/2019, it was observed '
'that the differential pressure gauge between the two rooms was not operating '
'properly, and the needle on the pressure gauge was resting on the pin '
'below the pressure gauge’s minimum scale reading of 0.0 inches of water . '
'You have also been documenting a reading of -0.01 inches of water as the '
'pressure reading between the ISO 7 Chemo Room and ISO 7 Ante Room on your '
'(5/5) “Temperature, Humidity, and Pressure Log,” which is a reading below '
'the capability of your differential pressure gauge. The documented pressure '
'reading does not indicate the actual daily pressure differential between the '
'ISO 7 Ante Room and the ISO 7 Chemo Room. Instead, - 0.01 inches of water '
'pressure is documented, which was the differential pressure between the two '
'rooms when the pressure between the rooms was last balanced approximately '
'one year ago. C. You failed to appropriately monitor the pressure '
'differential between the ISO 7 Clean Room and the ISO 7 Chemo Room. You '
'document 0.01 inches of water as the pressure reading between the ISO 7 '
'Clean Room and ISO 7 Chemo Room on youl() Ca} “Temperature, Humidity, and '
'Pressure Log,” when there is no pressure differential gauge installed '
'between the ISO 7 Clean Room and the ISO 7 Chemo Room. You document a 0.01 '
'inches of water pressure reading, which was the differential pressure '
'between the two rooms when the pressure between the rooms was last balanced '
'approximately one year ago. D. On 08/05/2019, the pharmacy replaced the '
'pressure differential gauge between the ISO 7 Ante Room and the ISO 7 Chemo '
'Room. On 08/05/2019, it was observed that the pressure gauge between the two '
'rooms indicated an Ante Room pressure of 0.025 inches of water was '
'opened, the needle on the pressure gauge was resting on the pin below the '
'pressure gauge’s minimum scale reading of 0.0 inches of water pressure. The '
'minimum acceptance criteria for the pressure differential between the two '
'rooms are is lost ')
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Firm Name: Hawaii Health Systems Corporation dba Kona Community Hospital Pharmacy
Record Date: 2019-12-13 00:00:00
Topic Probability: 0.9957447648048401
Observation:
('Your facility was designed and/or operated in a way that permits poor flow '
'of personnel and materials. Specifically, the design of the cleanrooms was '
'deficient in the following ways: a.) Smoke studies performed in the ISO 5 '
'Biological Safety Cabinet used to produce sterile hazardous drug products '
'were not conducted under dynamic conditions to show unidirectional airflow '
'during routine production operations. b.) HEPA filtered air supply vents '
'and air returns are all located on the ceilings of the ISO 7 Hazardous Drug '
'Room, ISO 7 Non-Hazardous Drug Room, and ISO 8 Ante Room. The metal air '
'vents are not designed to provide unidirectional air to the rooms with air '
'dispersing in two to four different directions from each vent. The firm has '
'not evaluated the air patterns in each room. c.) The ISO 7 Hazardous Drug '
'Room, ISO 7 Non-Hazardous Drug Room, and ISO 8 Ante Room share air handling '
'units ((b) (4) ) and a common final HEPA filter with the unclassified office '
'area of the pharmacy. There are no HEPA filters located directly at the air '
'supply vents to each ISO- classified room. d.) Operators entering the ISO 7 '
'Hazardous Drug Room must first enter the ISO 8 Ante Room to perform initial '
'gowning and pass through the ISO 7 Non-Hazardous Drug Room to enter the ISO '
'7 Hazardous Drug Room, where additional gowning and gloves are donned. On '
'12/03/19, we observed the operator go back and forth between the ISO 7 '
'Hazardous Drug Room and ISO 8 Ante Room on at least two occasions to obtain '
'more supplies needed for production and cleaning. Upon exiting the ISO 7 '
'Hazardous Drug Room, the secondary gowning was removed and redonned upon '
'reentry; however, there are no restrictions of products being made in both '
'rooms simultaneously and there has been no evaluation of the air patterns '
'created by the movement between rooms. e.) Room light fixtures located in '
'the ISO 7 Hazardous Drug Room, ISO 7 Non-Hazardous Drug Room, and ISO 8 Ante '
'Room protrude from the ceiling and are not completely sealed around the '
'edges. Gaps of approximately 1/8" in width were observed along the length of '
'each side of the various light fixtures in each room. ')
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TOPIC NUMBER 4
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Firm Name: Edge Pharma, LLC
Record Date: 2020-03-30 00:00:00
Topic Probability: 0.997157871723175
Observation:
('Aseptic processing areas are deficient regarding the system for monitoring '
'environmental conditions. Specifically, the firm’s environmental monitoring '
'practices of classified and aseptic processing areas do not ensure '
'appropriate levels of environmental cleanliness. For example: A. The firm '
'failed to conduct investigations of environmental excursions to include '
'microbial species identification and perform corrective and preventive '
'actions following identification of objectionable microbes recovered from '
'classified environments such as additional sporicidal cleanings. For '
'example, on 9/25/2019, the firm recovered airborne mold from two locations '
'in ISO-8 room 300 (the firm’s (B) (4) ) and airborne mold from 3 locations '
'in ISO-7 room 302 (the firm’s (b) (4) ); however, the firm failed to '
'initiate an EEI, only performed microbial species identification for 2 of '
'the 5 mold recoveries (Talaromyces wortmannii and Irpex lacteus, both '
'filamentous fungi), and failed to perform corrective actions such as '
'additional sporicidal cleanings. B. Objectionable microorganisms such as '
'mold and fungus are not identified to species level. For example, from '
'9/1/18 to 3/11/20 a total of 294 environmental monitoring sample recoveries '
'from classified environments were phenotypically identified as mold or '
'fungus and documented by the firm’s staff; however, only 270 of these '
'recoveries were microbially identified to species level. C. Not all ISO-5 '
'microbial recoveries are identified and investigated. The firm does not '
'perform microbial species identification on all recoveries found on '
'operator’s sleeves unless the recovery is CFUs. Operator’s sleeves were '
'observed to routinely enter ISO-5 environments during the inspection. From '
'4/1/19 to 12/31/19, the firm failed to conduct investigations including '
'microbial species identification on 73 microbial recoveries from operator’s '
'sleeves and it is unknown if these recoveries represent objectionable '
'organisms such as spore formers. D. The firm’s environmental monitoring '
'practices of the il (b) (4)iaminar flow hoods” @ FH) located in the firm’s '
'ISO-7 Clean Room 202 are not supported by scientific justification for '
'sampling locations. For example, the stainless-steel decks of the LFHs ((b) '
'(4) in dimension) are perforated with approximately (b) (4) diameter holes '
'except for an approximate (B) (4)-wide non-perforated strip of '
'stainless-steel surface located in the center of the deck. The firm was '
'observed to perform surface sampling of the perforated portion of the VLFH '
'deck instead of the uniform portion of the deck, therefore not allowing for '
'complete contact of sample media to the deck surface. E. The firm lacks '
'scientific rationale for environmental monitoring alert and action levels. '
'For example, the firm’s ISO-7 surface sampling alert level is ™@ CFUs and '
'action level is” CFUs, and the firm’s ISO-7 viable air alert level is ’CFUs '
'and action level is” CFUs. In addition, the firm does not perform EEIs to '
'include microbial species identification (firm personnel morphologically '
'identify mold and or fungus) and corrective actions for ISO-7 microbial '
'recoveries unless the recovery is ()4) CFUs for surface sampling o1!®) @) '
'CFUs for viable air sampling. It is unknown if these recoveries represent '
'objectionable organisms. F. The firm’s personnel monitoring practices are — '
'For example, on 3/6/20, two technicians were observed to spray their hands '
'witht )) (4) approximately 90 seconds prior to performing gloved fingertip '
'monitoring, and on 3/11/20 a technician was observed spraying their hands '
'with immediately before fingertip personnel monitoring. G. The firm’s '
'environmental monitoring personnel procedures and sampling methods are '
'inadequate and do not ensure recovery of microbes. For example, firm '
'procedure, S-QMR-008 — Personnel Monitoring, states “() (4) . — - On '
'3/6/2020 during a pump to syringe media fill a technician was observed to '
'quickly and lightly tap their fingertips on the agar surface while '
'performing gloved fingertip monitoring instead of (b) (4) with adequate '
'pressure to ensure recovery of potential microbes. Environmental monitoring '
'deficiencies were also noted during the 2014 and 2018 FDA inspections. ')
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Firm Name: Hawaii Health Systems Corporation dba Kona Community Hospital Pharmacy
Record Date: 2019-12-13 00:00:00
Topic Probability: 0.9971029162406921
Observation:
('You did not make adequate product evaluation and take remedial action where '
'actionable microbial contamination was found to be present in an area '
'adjacent to the ISO 5 classified aseptic processing area during aseptic '
'production. Specifically, actionable microbial contamination was discovered '
'inside (Db) (4) rooms, where the ISO 5 Biological Safety Cabinet (BSC) and '
'ISO 5 Laminar Airflow (LAF) Hood are located, during (B) (4) cleanroom '
'certifications and periodic settling plate samples and no evaluation of '
'product impact was made. For example: a.) During the 12/11/18 (b) (4) '
'recertification, the ISO 7 Non-Hazardous Drug Room Viable Air Sample, ID (®) '
'(4) had a calculated 44 colony forming units (cfu) /m? identified as '
'Coagulase-negative Staphylococcus species, Dermabacter hominis, and '
'Micrococcus luteus, and the ISO 7 Hazardous Drug Room Viable Air Sample, ID '
'(b) (4) had a calculated 18 cfu/m? identified as Bacillus species, '
'Micrococcus luteus, Micrococcus species, and Staphylococcus haemolyticus. '
'The firm did not evaluate any products filled in the ISO 5 LAF Hood and ISO '
'5 BSC on 12/11/18 for product impact, including but not limited to: Morphine '
'Img/mL SOmL, Vancomycin 750mg, Vancomycin 1000mg, Vancomycin 1250mg, '
'Vancomycin 1500mg, Acyclovir 600mg, Ertapenem 500mg, Ceftriaxone 473mg, '
'Azithromycin 94.6mg, Ampicillin 473mg, Vasopressin 40 units, and Azacitidine '
'150mg. On the 01/24/19 retest from the December recertification, the ISO 7 '
'Non-Hazardous Drug Room Viable Air Sample, ID (6) (4) had a calculated 27 '
'cfw/m? identified as C orynebacterium minutissimum, Corynebacterium species, '
'Micrococcus species, and Staphylococcus haemolyticus. The firm did not '
'evaluate any products filled in the ISO 5 LAF Hood on 01/24/19 for product '
'impact, including but not limited to: Octreocide 50mcg, Octreocide 500mcg, '
'Pantoprazole 80mg, Clindamycin 61.16lmg, Vancomycin 1000mg, Vancomycin '
'1250mg, Ampicillin 80mg, and Gentamicin 7.2mg. c.) On 01/29/19, a settling '
'plate located (b) (4) in the ISO 7 Non-Hazardous Drug Room had one colony of '
'mold, which was not identified. The firm did not evaluate any products '
'filled in the ISO 5 LAF Hood on 01/29/19 for product impact, which include: '
'Hydromorphone 0.2mg/mL, Midazolam Img/mL, Fentanyl 550mcg/S55mL, Vancomycin '
'750mg, Vancomycin 1250mg. Vancomycin 2000mg. and Ferric Carboxymaltose '
'750mg. On 03/27/19, a settling plate located (b) (4) of the ISO 7 Hazardous '
'Drug Room had 2 cfu that were not identified. The firm did not evaluate any '
'products filled in the ISO 5 BSC on 03/27/19 b. — d. — for product '
'impact, which include: Nivolumab 480mg, Pertuzumab 420mg, Trastuzumab 450mg, '
'Obinutuzumab 1000mg, Bendamustine 125mg. Leucovorin 564mg, Oxaliplatin '
'120mg, Fluorouracil 564mg, Fluorouracil 3384mg, Irinotecan 212mg. and '
'Carfilzomib 60mg. e.) On 05/28/19, a settling plate located (b) (4) 7 in '
'the ISO 7 Non-Hazardous Drug Room had one colony of yeast that was not '
'identified. The firm did not evaluate any products filled in the ISO 5 LAF '
'Hood on 05/28/19 for product impact, which include: Penicillin G 2.5 million '
'Units/Saline 1000mL, Gentamicin 340mg, and Vancomycin 1250mg. f.) During '
'the 06/05/19 (b) (4) __ recertification, the ISO 7 Hazardous Drug Room '
'Viable Air sample, ID (b) (4). had a calculated 56 cfu/m? identified as '
'Coagulase-negative Staphylococcus species, Corynebacterium minutissimum, '
'Corynebacterium tuberculostearicum, Corynebacterium-like bacteria, '
'gram-positive cocci, Micrococcus luteus, and Micrococcus species, and the '
'ISO 7 Hazardous Drug Room Surface Sample, ID (b) (4) had a calculated 9 cfu '
'on the plate identified as Cellumonas species, Coagulase-negative '
'Staphylococcus species, gram-positive rod, Micrococcus luteus, and '
'Staphylococcus saprophyticus. The firm did not evaluate any products filled '
'in the ISO 5 BSC on 06/05/19 for product impact, which include: Magnesium '
'Sulfate 6g/Saline 162mL, Vancomycin 750mg, Vancomycin 1000mg, Vancomycin '
'1250mg. Vancomycin 1500mg. Ampicillin/Sulbactam 3000mg. Potassium Phosphate '
'15mmol, Acyclovir 715mg. Nivolumab 240mg, Nivolumab 480mg, Leucovorin 600mg, '
'Leucovorin 664mg, Oxaliplatin 130mg. Oxaliplatin 141mg, Fluorouracil 600mg, '
'Fluorouracil 664mg, Fluorouracil 3700mg, Bevacizumab 585mg, and '
'Pembrolizumab 200mg. ')
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Firm Name: Advanced Nutriceuticals, LLC
Record Date: 2020-10-29 00:00:00
Topic Probability: 0.9954625964164734
Observation:
('Your employees touched equipment and other surface areas outside the ISO 5 '
'area with gloved hands and proceeded to aseptically process drug product '
'without changing or sanitizing gloves. Specifically, On 10/14/2020 and '
'10/16/2020, we observed your sterile technician perform aseptic techniques '
'in the ISO 5 Cleanroom hood. Your sterile technician’s practice of '
'sanitizing sterile gloved hands and changing of gloves in between contacting '
'non-sterile and sterile materials is inadequate. For example: A) On '
'10/16/2020 while aseptically processing Selank 1000MCG/ML 5 ML, LOT '
'1016202002 EXP 11/16/2020 from non-sterile to sterile in the ISO 5 Cleanroom '
'hood: 1. We observed your sterile technician touch or retrieve items '
'outside the ISO 5 Cleanroom hood a total of fourteen (14) times. These '
'include touching the staging cart handle bar, retrieving vials from a '
'non-sterile (4) bag outside the ISO 5 area, and retrieving a syringe outside '
'the ISO 5 area. In between retrieving items from outside of the ISO 5 area, '
'we observed your employee sanitize their gloved hands only once. 2. We '
'observed your sterile technician adjusted their face mask in between aseptic '
'(b) (4) with gloved hands in the ISO 5 Cleanroom hood. This employee did not '
'sanitize their gloved hands after touching the face mask. 3. We observed '
'your sterile technician’s gloved hands were visually contaminated and wet '
'with drug product while attaching a (b) (4) to a syringe which contained '
'product. After the gloves were contaminated, your sterile technician did not '
'don a new pair of gloves and only sanitized this contaminated glove with '
'sterile before proceeding to aseptically (MAY Selank LOT 1016202002 EXP '
'11/16/2020 from non-sterile to sterile in the ISO 5 Cleanroom hood. B) On '
'10/14/2020, we observed your sterile technician grabbing the trash bin '
'located outside the ISO 5 area with their gloved hands. Your sterile '
'technician neither donned a new pair of sterile gloves nor sanitized their '
'gloved hands before returning to admix a Myer’s Cocktail IV bag in the ISO '
'5 Cleanroom hood. Your sterile technician added the 1 but not limited to '
'Ascorbic Acid LOT EXP 11/20/2020, Potassium Phosphate LOT EXP '
'11/10/2020, Glutathione LOT EXP 11/18/2020, and B Complex LOT EXP 11/28/2020 '
'into an IV bag in the Cleanroom hood on 10/14/2020. ')
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TOPIC NUMBER 5
===============================================================================
Firm Name: Novel Laboratories, Inc. d.b.a LUPIN
Record Date: 2020-11-05 00:00:00
Topic Probability: 0.9971585273742676
Observation:
('Laboratory controls do not include the establishment of scientifically sound '
'and appropriate test procedures designed to assure that drug products '
'conform to appropriate standards of identity, strength, quality and purity. '
'Specifically, A. There are no procedures to ensure that the Karl Fischer '
'(KF) Moisture Analyzer operates as intended and can accurately assess water '
'content for release testing of the Raw Materials and Finished Products. The '
'firm’s SOP NL-QC-039.15 “OPERATION AND CALIBRATION OF THE KARL FISCHER '
'AUTO-TITRATOR AND POTENTIOMETRIC AUTO-TITRATOR” Effective Date 06/09/2020 '
'does not require analysis of a standard that is close to the sample results '
'for an accuracy check. Instead, the firm uses water to conduct the accuracy '
'check with an acceptance specification of However, the QC water content '
'specification for numerous samples is smaller than the range of error for '
'the water accuracy check. In addition, the firm currently only performs '
'accuracy at of the during the calibration of instrument. The intended used '
'is between therefore, the accuracy needs to be performed at different (b) '
'(4) during the instrument calibration for accuracy of the: The water '
'content specifications for following API, Raw Materials, and Finish '
'Products: Product Water Content Specification Potassium Chloride '
'for Oral Solution, USP NMT PEG-3350, Sodium Sulfate, Sodium Chloride, NMT '
'Potassium Chloride, Sodium Ascorbate and Ascorbic Acid for Oral Solution '
'(Generic )@) > Polyethylene Glycol for Oral Solution '
'(GaviLax) NM’ Quinapril HCL NMT Somerset, NJ 08873-1145 [| Drug Product '
'Manufacturer NMT nazole, USP NM’ PEG-3350 '
'NMT. B. Your written procedure for '
'calibration of pH meters SOP NL-QC-035.8 “OPERATION, CALIBRATION AND '
'STANDARDIZATION OF pH METERS” Effective Date 03/04/2020, which is used to '
'measure pH in the preparation of mobile phases and diluents, Raw Material '
'release testing, in-process testing, and Finished Product release testing of '
'drug products, is deficient in that: 1. pH probe thermometers are not '
'calibrated as part of the calibration procedure nor are they verified at '
'time of use to ensure that they are reading the correct temperature when the '
'pH is taken. As a result, there is no assurance that the pH readings, which '
'are temperature dependent and automatically adjusted by the instrument, are '
'accurate. 2. During calibration of the pH probe, which is done at least '
'(BJ{@J, the temperature and offset are not monitored or recorded. C. Your '
'written procedure for calibration of HPLC SOP NL-QC-031.16 “OPERATION AND '
'CALIBRATION OF HIGH PERFORMANCE LIQUID CHROMATOGRAPHS” Effective Date '
'02/21/2020, which is used to perform analyses for Assay, Dissolution, and '
'Related Compound of Raw Materials, In-Process, Finish Product, and '
'Stability Samples, is deficient in that the ow calibration only checks the '
'air temperature of the in one location (exact location not noted in '
'calibration document). There is no Somerset, NJ 08873-1145 Drug Product '
'Manufacturer assurance that the (EE is able to maintain SITS across '
'the (ey) vial locations within the instrument. The test methods for the '
'following products require a specific temperature for the sample solution '
'prior to injection: Method # (6) (4) Title Temperature '
'RM-I16561-LC-HCOOH | - Method of Analysis for (B49) RM-116561-LC-HCHO '
'~ Method of Analysis for (N40 FP-834269-LC-RC FP-060-DEG Azithromycin '
'Tablets, USP- and| for Oral Solution, USP FP-358-LC-AS Hydrocodone '
'Bitartrate and Acetaminophen Tablets, USP — FP-358-LC-RC Hydrocodone '
'Bitartrate and Acetaminophen Tablets, USP — FP-123-AS-02 '
'i LLL OL FP-123-DEG-00 Temazepam Capsules, Temazepam Capsules, USP — ')
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Firm Name: Novel Laboratories, Inc. d.b.a LUPIN
Record Date: 2020-11-05 00:00:00
Topic Probability: 0.9970352649688721
Observation:
('Written procedures are not followed for evaluations done at least (S)(@YM '
'and including provisions for a review of complaints, recalls, returned or '
'salvaged drug products, and investigations conducted for each drug product. '
'Specifically, control procedure for Annual Product Review (SOP No. '
'NL-QA-042.7, Version: 7, Effective Date: 4/26/2018) is not followed to '
'evaluate the products at least annually. Somerset, NJ 08873-1145 [ Drug '
'Product Manufacturer The review cycle for each drug product (based on '
'approval of the ANDA) is defined in Annual Product Review SOP. As per this '
'SOP the annual product review report should be completed after (BRAVE of the '
'review cycle. On 9/30/2020, significant deficiencies pertaining to timely '
'completion of annual product review reports were observed as '
'below: 7 Total products for | # of products with # of '
'products with review Review Cycle 7 ? é review delayed review still pending '
'20 Gi) 18 @§%) 39) 20 i) 36 @%) 0 @%) As of 9/30/202, the '
'Quality Unit failed to complete the annual review for about fff products for '
'more than (B® as below: a Number '
'of Produc Nome come | Magee | eee | See PP Delayed Potassium Chloride ER '
'Tablets 10 SHANG NS mEqK and (Sa 01/20/2019 09/29/2020* a 12/8/2017 to '
'Phenelzine Tablets, 15mg Denote 05/29/2019 Hydrocodone Bitartrate and '
'Homatropine Methylbromide an eg Pending Tablets, Smg and 1.5mg Review '
'Tinidazole Tablets, USP 250 mg & | 4/30/2018 to Pending 500 mg_ 4/29/2019 '
'Review Methylergonovine Tablets, USP 0.2 | 5/2/2018 to Pending L mg 3/1/2019 '
'Review Temazepam Capsules, USP 15 mg, | 4/21/2018 to 7.5mg, 22.5 mg, 30mg '
'4/20/2019 09/11/2020* EEE EERE EEEEeeeee ees '
'06/15/2018 Pending to 6/14/2019 Review 06/19/2018 Orphenadrine ER Tablets, '
'100mg to Pending 06/18/2019 Review : 05/27/2018 Gavitye to 5/26/2019 '
'09/09/2020* Somerset, NJ 08873-1145 | Drug Product Manufacturer a 6/1/2018 '
'to Saibpes 5/31/2019 09/12/2020* a 6/01/2018 to Seabee 5/31/2019 09/11/2020* '
'Doxycycline capsules, 50, 75, and | 5/28/2018 to Pending 100mg 5/27/2019 '
'Review Voriconazole for Oral 5/31/2018 to Trimethoprim Tablets, '
'100mg Zolpidem Tartrate Sublingual 6/3/2018 to Pending Tablets, '
'1.75 & 3.5 mg 6/2/2019 Review Suspension,40mg/SmL 5/30/2019 09/09/2020* '
'07/07/2018 si * Flucytosine Capsules 250 mg and oa Pending aoe: 07/06/2019 '
'Review Oxycodone HCI Oral Solution, 4/29/2018 to 20mg/ml 4/28/2019 '
'07/17/2020 Misoprostol Tablets, 100 mcg & 200 | 7/25/2018 to Pending meg. '
'7/24/2019 Review Nystatin Topical Powder, 100,000 | 7/23/2018 to Units/g, '
'7/22/2019 09/29/2020* Pentazocine and Naloxone HCl T/N//2018 to Tablets, '
'50/0.5 mg CIV 7/10/2019 09/09/2020* *Review completed during inspection or '
'after inspection announced '
'Specifically, Your written procedure for laboratory analyst training SOP '
'NL-QC-002.3 “TRAINING OF LABORATORY PERSONNEL” Effective Date 08/11/2014 '
'does not contain a standard training procedure in place for the laboratory '
'analysts for consistent On-the-Job (OJT) training to assure that all '
'analysts receive similar training. Instead, the SOP states that “Assessment '
'of instrument skills based on past experience” and “Extent of Hands-on eee '
'necessary will be determined on the basis o: (LT ac OJTs for a new employee '
'with previous experiences are skipped. During review of training records for '
'{MJ analysts, no OJT records were available. Instead, a Memo was provided '
'for one of the analysts stating that “practical training” had been given on '
'various instruments: Karl Fischer, UV-Vis, Dissolution, HPLC, GC, Density '
'Meter, and Viscometer however, no records of “practical training” were '
'documented and the SOP does not explain what “practical training” consists '
'of. *DATES OF INSPECTION 09/10/2020(Thu), 09/1 1/2020(Fri), '
'09/14/2020(Mon), 09/15/2020(Tue), 09/16/2020( Wed), 09/17/2020(Thu), '
'09/18/2020(Fri), 09/24/2020(Thu), 09/25/2020(Fri), 09/28/2020(Mon), '
'09/29/2020(Tue), 09/30/2020(Wed), 10/01/2020(Thu), 10/06/2020(Tue), '
'10/07/2020( Wed), 10/08/2020(Thu), 10/20/2020(Tue), 10/21/2020(Wed), '
'Somerset, NJ 08873-1145 l Drug Product Manufacturer a ')
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Firm Name: Fusion IV Pharmaceuticals, Inc. dba Axia Pharmaceuticals
Record Date: 2019-12-20 00:00:00
Topic Probability: 0.9967412948608398
Observation:
('Laboratory controls do not include the establishment of scientifically sound '
'and appropriate test procedures designed to assure that conform to '
'appropriate standards of identity, strength, quality and purity. '
'Specifically, A. Growth Promotion testing of the OI used in the Aseptic '
'Process Simulations are challenged with only two organisms; Bacillus '
'subtilis and Candida Albicans. The testing of only two organisms does not '
'demonstrate the media can support growth of a wide range of microorganisms. '
'Your firm is not following the Policy on Aseptic Process Simulations as '
'stated in SOP 4.72 section 8.4.8 which states the selection of 5 '
'microorganisms. B. Your firm has not performed an antimicrobial '
'effectiveness study to verify that the preservative system is effective and '
'protects the product over its shelf life under expected conditions of use. '
'For example, the following drug stock solutions have a shelf life of six '
'months and contain a preservative. You have not verified through '
'antimicrobial effectiveness studies the content of the preservative. In '
'addition, stability studies have not been provided to show the drug product '
'is stable in its container. Papaverine HCL; lot 10142019+53116, discard '
'after April 11, 2020 Phentolamine Mesylate; lot 10142019+53114, discard '
'after April 11, 2020 This is a repeat objectionable observation from the '
'March 2017 FDA inspection. Your firm’s manual visual inspection is '
'inadequate and does not ensure your drug product is contamination free prior '
'to distribution. 1. I observed on 12/5/2019 in the cleanroom suite (ISO 7), '
'aseptic fill technician performing visual inspections at a metal table on '
'finished drugs vial without assistance from light magnification or '
'contrasting white background. I observed the fill technician hold the vial '
'O@9yyyand shake the vial MY hen label the vials. The fill technician '
'conducted visual inspection and labeling on the following drug lots: '
'Alprostadil 150 meg/ml lot 12042019+53331 Papaverine HCL/Phentolamine '
'mesylate 60mg/40mg/ml lot 12042019+53329 Alprostadil/Papaverme '
'HCL/Phentolamine mesylate/Atropine 18mcg/1.8mg/0.2mg/0.2mg/ml _ lot '
'12042019+53327 Alprostadil/Papaverme HCL/Phentolamine mesylate/Atropme '
'40mcg/25mg/0.5mg/0.lmg/ml _ lot 12042019+53325 Alprostadil/Papaverine '
'HCL/Phentolamine mesylate/Atropine 60mcg/30mg/2mg/0.15mg/ml lot '
'12042019+53323. 2. On 12/5/2019 in the visual inspection room, I observed '
'an employee maneuver Triamcinolone Acetonide (Preservative Free) 2 ml vials '
'lot 12032019+53303 onto the table for labeling and inadvertently drop a vial '
'on the concrete floor. He picked up the vial held it up for approximately '
'one second to the light asked the process engineer if it was ok. The process '
'engineer nodded and the employee placed it back on the table for labeling. '
'There was no additional examination of the integrity of the glass vial. This '
'visual inspection practice does not adhere to your firm’s SOP 2.87, titled, '
'‘Visual Inspection of Finished Drug Products” section 8.5.2 that “if the '
'inspector is uncertain about a potential defect, the unit should be '
'segregated and evaluated more thoroughly by another qualified inspector '
'and/or a Quality Unit representative...” 3. Prior to the fo ll visual '
'inspection of Triamcinolone Acetonide (Preservative Free) 2 ml vials lot '
'12032019+53303, your firm failed to measure the intensity of the light '
'source using a calibrated on the visual inspection machine. SOP 2.87, '
'titled, ‘Visual Inspection of Finished Drug Products” section 8.4 requires '
'the measurement to be recorded in the batch production record; however, '
'there is no allotted space in the batch record to record this measurement. ')
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===============================================================================
TOPIC NUMBER 6
===============================================================================
Firm Name: Fusion IV Pharmaceuticals, Inc. dba Axia Pharmaceuticals
Record Date: 2019-12-20 00:00:00
Topic Probability: 0.9982351660728455
Observation:
('Procedures designed to prevent microbiological contamination of drug '
'products purporting to be sterile are not followed. Specifically, A. '
'Observed on 12/3/2019, during the aseptic processing of Methylpredinsolone '
'Acetate batch 12022019+53297, technician dispensed from the ie | bag onto '
'the table top of the laminar flow workstation and use each vial (Theoretical '
'yield ™™ unit vials). Your firm is not followmg your standard operating '
'procedure document number 4.71 titled, “Aseptic Processing Requirements and '
'Technique” which reads in section 7.1.10, “Compounding personnel shall not '
'use a gloved hand to touch any product contact surfaces, but should use '
'appropriately sterilized utensils (e.g., forceps), as needed.” B. '
'Observed on 12/11/2019 in the ISO 5 aseptic filling room, aseptic filling '
'operator performed Pee interventions during the ‘it filling of Glutathione '
'batch 12102019+53365 without routinely sanitizing hands. I observed the '
'operator open the cabinet door of the filling machine (ISO 5) and perform '
'interventions at least nissan stopping and starting the machine, dispensing '
'components in the hopper, manipulate capped vials inside the filling machine '
'for approximately a ae period. Your firm is not following your standard '
'operating procedure document number 4.71 tiled, “Aseptic Processing '
'Requirements and Technique” which reads in section 7.1.11, “Compounding '
'personnel shall change sterile gloves on a frequent basis or disinfect them '
'routinely with OI during prolonged compounding manipulations.” C. You did '
'not perform investigations into the root cause of media fill sterility '
'failures for media fill runs performed in ISO 5 Laminar Flow Workstations '
'(LAFWs) from Pe. Turbidity was observed in the solutions. You failed to '
'investigate the root cause for the following media fill failures prior to '
'producing and distributing sterile products. See four examples found below: '
'1 Run cil (ail syringe); Summary report PO) RPT notes the following fill '
'runs passed: Resa However, the “Summary of Validation '
'Discrepancies” reads “there was a failure noted”. Media fill number @ 5 is '
'noted as failed. Your firm failed to investigate the failure per your SOP '
'4.80, titled, “Validation Protocol for Aseptic Process Simulations”. It '
'reads in section 9.1.1.1., “Any positive units, deviations, or discrepancies '
'must be investigated and shown to have no impact on the validation. In '
'addition, your firm could not provide the batch production record for this '
'failed trial run a: Run Type sail Onl vial); Summary report Ln RPT notes '
'the following media fill runs passed: The “Summary of '
'Validation Discrepancies” reads “there was a failure noted”. The summary '
'report does not list the failure. However, it was found media fill run me] '
'PRD contained the failure. The batch production record for media fill run '
'PO) POW reads the media solution was aseptically The solution “turned turbid '
'after 2 and was not filled into the vials”. Media fill run was replaced with '
'media fill Your firm failed to investigate the failure per your SOP '
'4.80, titled, “Validation Protocol for Aseptic Process Simulations”. It '
'reads in section 9.1.1.1., “Any positive units, deviations, or discrepancies '
'must be investigated and shown to have no impact on the validation. 3. Run '
'Typ validation 2@ 7) filling machine Aseptic Processing Simulation (al '
'vial); Summary report RPT notes the following fill runs passed: The '
'“Summary of Validation Discrepancies” reads “there was a failure noted”. The '
'summary report does not list the failure. Your firm failed to investigate '
'the failure per your SOP 4.80, titled, “Validation Protocol for Aseptic '
'Process Simulations”. It reads in section 9.1.1.1., “Any positive units, '
'deviations, or discrepancies must be investigated and shown to have no '
'impact on the validation. 4. Run Typ mo vial); Summary report = | RPT notes '
'the following media fill runs passed: The “Summary of Validation '
'Discrepancies” reads “there was a failure noted”. The summary report does '
'not list the failure. However, it was found media fill run ) contained the '
'failure. The batch production record for media fill run eee 3) reads “AP has '
'been cancelled due to turbidity of solution after approximately in room '
'temperature.” Media fill run was replaced with media '
'fill Your firm failed to investigate the failure per '
'your SOP 4.80, titled, “Validation Protocol for Aseptic Process '
'Simulations”. It reads in section 9.1.1.1., “Any positive units, deviations, '
'or discrepancies must be investigated and shown to have no impact on the '
'validation. Failure to perform investigations into the root cause of media '
'fill sterility failures for media fill runs is a repeat objectionable '
'observation listed on the FDA 483 inspection dated March 2017. D. All '
'media vials from the Aseptic Process Simulation are not being incubated. For '
'example; the Aseptic Processing simulations for th ial filler Report ID# '
'details Run POW lot number III yielded a) ] vials; however onl were '
'incubated. Run lot numbe ielded Pe only PA vials were incubated. Ruy lot '
'number ielded vials only? vials incubated. Justification provided in the '
'batch record stated it was due to “space constraints”. Therefore, your firm '
'selected every 20) vial to be incubated. EB. Your firm is not '
'following SOP 3.40 Cleaning and Disinfection in Sterile Compounding Areas, '
'version 4 section 4.3. Quality Unit is responsible for reviewing '
'documentation of the cleaning of the contracted cleaning personnel '
'performing the cleaning of the cleanroom suites and laminar flow '
'workstations. There is no review by signature on they cleaning logs '
'completed by the cleaning contractor for the months of October and November '
'2019. There is no Check By signature on the an cleaning logs completed by '
'the cleaning contractor for the months of October and November 2019. ')
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Firm Name: Hospira Inc
Record Date: 2020-01-17 00:00:00
Topic Probability: 0.9973527193069458
Observation:
('Written records of investigations into unexplained discrepancies do not '
'always include the conclusions and follow-up. Specifically, A. On August '
'21, 2019, an NDA Field- Alert Report McPfar# 2019-043 was initiated for the '
'recovery of 2 species of mold (Cladsporium species and Sarocladium '
'terricola) equaling 62 cfu from the multi-product aseptic filling lin ®)@ '
'Grade A zone where lyophilized product is transferred to the lyophilizer '
'trayer. Furthermore, 6 cfu of bacterial colonies (Brachybacterium rhamnosum) '
'were recovered from the Grade A zone from the same settle plate. In '
'addition, on August 16, 2019, a recovery of 2 cfu of mold colonies '
'(Aspergillus species) were isolated from the personnel/material Grade B (b) '
'(4) Grade A/B aseptic area. The mold and bacteria recoveries were '
'identified in the Grade A aseptic zone where lyophilized and sterile '
'solutions are produced. The firm has failed to identify product associated '
'within the filed NDA Field- Alert. However, according to PR#4138900, there '
'wer (6) (4) lots manufactured during the time of the event and (6) (4) lots '
'were released into market. Excursions were due to a missed cleaning and room '
'pressure excursions. B. On 12/02/2018, an NDA Field-Alert Report McPfar# '
'2019-150 was initiated for the recovery of 2 species of mold (Tritirachium '
'oryae and Asperigillus sydowii) equaling 14 cfu from the multi- product '
'aseptic filling lin ()()Grade A zone where the aseptic solution connection '
'is performed. Investigation PR# 2514531 determined that there was no impact '
'to Plazomicin Lot# 951003F and released the batch. Root causes and '
'corrective actions are not robust to mitigate risk and re- occurrence. C. '
'On 08/06/2019, an ANDA Field-Alert Report McPfar #2019-037 was initiated for '
'the recovery of 1 cfu of mold growth found on a viable passive air site in '
'the Grade A(6)(4) isolator on July 26, 2019. Investigation PR#4097952 '
'rejected Glatiramer Acetate Injection 20 mg/mL, Lot 070653F. However, the '
'investigation failed to implement an effective CAPA to control contamination '
'within the aseptic isolator barrier Grade A zone. D. Investigation PR# '
'4146395 failed to adequately address the air reversal excursions affecting '
'Grade A/B (b) (4) (room 338A) from the Grade D area supporting the asepti ©) '
'filling line. The room air pressure increases when Grade D room doors are '
'open at the same time as the Grade B doors leading to the asepti ®) filling '
'area. Corrective actions implemented did not mitigate future occurrences E. '
'On 12/22/2018, Field Alert McPfar 2018-169 was initiated for 23 cfu of mold '
'contamination detected inside a HEPA car (b) (4), used to transport aseptic '
'product from th © filling line. The field alert did not indicate that '
'Vancomycin Hydrochloride for Injection, Lot 96170DD was implicated and later '
'rejected as a batch disposition. Furthermore, the the Field Alert and CAPA '
'PR#2543245, failed to evaluate the (Db) (4)sanitation process of the HEPA '
'carts from the dates of closure, June 2019, to address the interim process '
'that will be used to mitigate risk. HEPA Carts are still being (b) (4) '
'sanitized to be reintroduced back into the clean rooms. F. On 01/23/2019, '
'Field Alert Report McPfar 2019-006 was initiated in response to '
'investigation PR#4322158 initiated for lcfu for a Class 1, Grade A personnel '
'that was working in the Grade A zone o © filling line. The investigation '
'identifies the cause of the mold species being due to gowning. However, the '
'firm has failed to implement appropriate corrective actions that prevent '
'mold excursions identified on Class 1 employee working inside a Grade A '
'zone. All product batches associated with this personnel excursion were '
'released for distribution. G. The firm has not initiated an overall '
'effective corrective action plan to mitigate the re-occurrence of bacterial '
'and/or mold colonies isolated from points throughout the aseptic '
'manufacturing suites and supporting areas. Since the last inspection in '
'August 2018, the firm continues to recover bacterial and/or mold isolates '
'from critical zones Grade A and B, supporting areas, and Class 1 '
'personnel. ')
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Firm Name: Legacy Pharmaceutical Packaging LLC
Record Date: 2020-01-16 00:00:00
Topic Probability: 0.9959757924079895
Observation:
('A process whose results cannot be fully verified by subsequent inspection '
'and test has not been adequately validated according to established '
'procedures. Specifically, the following was noted from review of the Final '
'Report for Performance Qualification for | Packaging (b) (4), dated on or '
'about 12/23/19: A. The process control verification protocol (QP '
'19-416,-417 and -418, part 8.0) documents the Vision System Challenge tests '
'for incorrect/illegible carton part code and /or UDI barcode on the carton '
'label was a critical quality classification. The final report-(part 4.0) '
'reads.as follows: “*** Ail PQ tests of the *** Vision System with *** '
'camera arid critical quality attribute checks were performed, verified and '
'demonstrated to meet all acceptance criteria***”. i. However, the vision '
'system atin as described in part 9 of the (b) (4) packaging instructions '
'(Document Number MBR-0602, revision 01), does not include using a challenge '
'carton with either an incorrect carton part code or incorrect UDI barcode. '
'The packaging project manager stated the optical character recognition (OCR) '
'capability of the vision system was never tested (challenged) to detect and '
'reject incorrect part codes or incorrect UDI bar codes during any of the (b) '
'(4) performance qualification (PQ) lots. . ii. | He said the vision system '
'was challenged: for missing / illegible codes, only. The challenge devices '
'for missing / illegible codes were not a controlled/standardized set of test '
'articles used for all performance qualification (PQ) lot tests. The test '
'articles were (b) (4) to each challenge S saul lot (b) (4) vision '
'challenges were performed per lot). B. The final report (part 5.0) reads-as '
'follows: “There were no exceptions initiated during the — execution of the '
'PQ protocols”. However Sane occurred and were not included in the final PQ '
'evaluation: i. | Maintenance was required to adjust the vision system during '
'(b) (4) production lot number (b) (4). The engineering technician said he '
'adjusted® on the vision system because the-system was rejecting too many '
'packages. This maintenance activity was not documented or evaluated as a '
'process exception in the final report. ii. | Vision system labeling rejects '
'was a statéed critical quality attribute check for the performance '
'qualification, however the number of labeling rejects (nonconformances) '
'detected were not recorded or evaluated as process exceptions in the final '
'report. iii. | The packaging project manager stated rejected/mislabeled '
'cartons were reworked during (b) (4) of the production lots: However, the '
'amount of rework was not recorded or included the final report as a process '
'exceptions. ')
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===============================================================================
TOPIC NUMBER 7
===============================================================================
Firm Name: SCA Pharmaceuticals
Record Date: 2019-11-19 00:00:00
Topic Probability: 0.9985273480415344
Observation:
('There is a failure to thoroughly review any unexplained discrepancy and the '
'failure of a batch or any of its components to meet any of its '
'specifications whether or not the batch has been already distributed. '
'Specifically, The firm failed to adequately investigate the following: A. '
'There have been seven confirmed failures for in-house sterility testing of '
'finished sterile drug products since October 2018 using a(b) (4) method for '
'detection of fluorescence in individual microorganisms ((b) (4) ). All '
'associated batches (1218003930, 1219007440, 1219008117, 1219008696, '
'1219009160, 1219009289, & 1219012541) were rejected; however, the '
'investigations did not take into account the identity of the contaminating '
'microorganism(s) to determine its source. For example: e '
'Out-of-Specification Laboratory Investigation Report OOS 18-087-W was '
'initiated on 10/15/2018 for the sterility test failure of Buffered Lidocaine '
'1% in Sodium Bicarbonate 8.4% (b) (4) Syringe lot number 1218003930. The '
'potential root cause(s) was determined to be human error; however, the '
'investigation did not identify the contaminating microorganism(s). The '
'investigation was approved by Quality Assurance 12/10/2018. e '
'Out-of-Specification Laboratory Investigation Report OOS 19-049-W was '
'initiated on 03/22/2019 for the sterility test failure of Buffered Lidocaine '
'1% in Sodium Bicarbonate 8.4% (b) (4) Syringe lot number 1219007440. A '
'definitive root cause had not been determined but the Deviation '
'Investigation (DV-19-312-W) indicated the possible root cause was human '
'error; however, the investigation did not identify the contaminating '
'microorganism(s). The investigation was approved by Quality Assurance on '
'06/17/2019. e Out-of-Specification Laboratory Investigation Report OOS '
'19-055-W was initiated on 04/18/2019 for the sels test failure of Ob) ( hone '
'HC] 0.2mg/mL in 0.9% Sodium Chloride( b) (4 \\b) (4) ) (4) lot number '
'1219008117. The potential root cause | in eee Investigation (DV-19- 385-W) '
'was human error; however, the investigation did not identify the '
'contaminating microorganism(s). The investigation was approved by Quality '
'Assurance on 09/05/2019. e Out-of-Specification Laboratory Investigation '
'Report OOS 19-066-W was initiated on 05/11/2019 for the sterility test '
'failure of Vancomycin HCI 1.25g added to 0.9% Sodium Chloride (b) (4) lot '
'number 1219008696. The potential root cause identified in Deviation '
'Investigation (DV-19-472-W) was human error; however, the investigation did '
'not identify the contaminating microorganism(s). The investigation was '
'approved by Quality Assurance on 08/05/2019. e Out-of-Specification '
'Laboratory Investigation Report OOS 19-071-W was initiated on 05/28/2019 for '
'the sterility test failure of Glycopyrrolate 0.2mg/mL (b) (4) Syringe(b) (4) '
'lot number 1219009160. The potential root cause identified in Deviation '
'Investigation (DV-19-553-W) was human error; however, the investigation did '
'not identify the contaminating microorganism(s). The investigation was '
'approved by Quality Assurance on 08/30/2019. e Out-of-Specification '
'Laboratory Investigation Report OOS 19-074-W was initiated on 05/31/2019 for '
'the sterility test failure of Phenylephrine HCl 40mcg/mL in 0.9% Sodium '
'Chloride (b) (4) Syringe (b) (4) lot number 1219009289. The potential root '
'cause identified in Deviation Investigation (DV-19-554-W) was human error; '
'however, the investigation did not identify the contaminating '
'microorganism(s). The investigation was approved by Quality Assurance on '
'08/30/2019. e Out-of-Specification Laboratory Investigation Report OOS '
'19-123-W was initiated on 09/25/2019 for the sterility test failure of Me '
'HCl 100mcg/mL in 0.9% Sodium Chloride (6) (4) Syringe (b) (4) lot number '
'1219012541. A definitive root cause had not been determined but the '
'Deviation Investigation (DV- 19-810-W) indicated the possible root cause was '
'human error; however, the investigation did not identify the contaminating '
'microorganism(s). The investigation was approved by Quality Assurance on '
'10/18/2019. Furthermore, it was noted that from January 2019 to October 2019 '
'the firm had approximately 105 occasions in which Personnel Exit Monitoring '
'had exceeded the action limit specification for zero objectionable organisms '
'mostly concerning samples taken from operator hoods (32 occurrences) and '
'chests (50 occurrences); however, the firm had not identified a potential '
'cause for this trend until the Environmental and Personnel Monitoring (b) '
'(4) Trend Report which was approved by Quality on 10/29/2019 during the '
'inspection. Examples of the objectionable organisms recovered were Bacillus '
'cereus, Staphylococcus aureus, Moraxella osloensis, and Roseomonas mucosa. '
'B. On 08/14/2019 the firm had initiated an Out-of-Specification '
'Investigation Report OOS-19- 111-W for a potency failure for the T90 (90 '
'days) stability sample of Heparin Sodium 10units/mL in 0.9% Sodium Chloride '
'(b) (4) _ lot number 1219008741, result 82%, specification (b) (4)%. The OOS '
'result was confirmed and the firm had initiated a Deviation Investigation '
'(DV-19-711-W) on 08/15/2019 to investigate this failure. The firm had Na) '
'the root cause as inconclusive and took the following corrective actions: (b '
'(4 _ The firm had not conducted a health hazard evaluation of the '
'sub-potent product nor had they notified the customers who had received OM '
'lots of this product with the 90 day BUD, some of which are currently within '
'expiry. c. On 08/16/2019, the firm initiated a Deviation Investigation '
'Report DV-19-716-W to espeate — within the (6) (4) (b) (4) assembly (SCA '
'part# (Db) (4)) at the (b) (4) side during (| b) (4) testing. The im '
'isolated this leaking (®) @)to one lot of ©) (lot number (b) (4) » This) '
'@)iot was used to manufacture ™™ batches of products in which ~ batches had '
'(aye istributed. The investigation indicated that the leaking would occur '
'between(b) (4 The firm concluded that based on investigational testing, '
'ster te testing, successful ib) (4) testing and risk assessment that the '
'leaking of the (6) (4) (©) @ had no impact to patient safety; however, the '
'firm had not provided samples from the lot of defective (b) (4) (©) (4)... '
'their vendor for evaluation and confirmation that the’ (b) (4) would '
'function as designed. The manufacturer of the (b) (4)(b) (4) 4)(b) ( ) (4) '
') had provided a written assessment of the functionality of the (®) @) on '
'October 21, 2019 (during the inspection) without an evaluation of this lot '
'of defective(b) (4) D. The Quality Unit failed to adequately investigate '
'consumer complaints by not evaluating retentions samples and returned '
'product when applicable for confirmation of the reported complaint. For '
'example: e Customer Complaint Form CUS-18-189-W, dated 11/13/2018, '
'indicated that a customer called stating the nurse from the floor was '
'reporting more hemorrhages on the L&D floor than normal. They had five '
'patients in one day hemorrhage. The customer was requesting potency data on '
'Oxytocin 20units added to 0.9% Sodium Chloride 1000ml Bag lot number '
'1218004043. The investigation concluded that there was no impact to product '
'identified as the potency of lot number 1218004043 was confirmed to be '
'within specification via batch record review. The firm did not conduct an '
'evaluation of retain samples. The investigation was approved by Quality on '
'12/27/2018. e Customer Complaint Form CUS-19-028-W, dated 2/26/2019, '
'indicated that a customer had administered © different ba gs of Oxytocin '
'20units added to 0.9% Sodium Chloride 500mL Bag lot number 1219006051 to ©) '
'@)different pregnant patients and in which their cervixes did not dilate '
'after receiving this product. The investigation concluded that there was no '
'impact to product identified as the potency of lot number 1219006051 was '
'confirmed to be within specification via batch record review. The firm did '
'not conduct an evaluation of retain samples. On 05/22/2019 the firm '
'received) @nnits from lot number 1219006051 from their customer. The units '
'were not evaluated but instead were destroyed. The investigation was '
'approved by Quality on 04/03/2019. e Customer Complaint Form CUS-19-051-W, '
'dated 04/25/2019, indicated that a customer stated that Oxytocin 20units '
'added to 0.9% Sodium Chloride 1000mL Bag lot number 1219007516 was not '
'working on patients. The investigation concluded that there was no impact to '
'product identified as the potency of lot number 1219007516 was confirmed to '
'be within specification via batch record review. The firm did not conduct an '
'evaluation of retain samples. The investigation was approved by Quality on '
'05/20/2019. Furthermore, the firm has had sixteen Out-of-Specification '
'Investigations involving sub- potent Oxytocin 20 and 30 unit products '
'compounded from October 2018 to March 2019. Each of these investigations '
'confirmed the potency out-of-specification result and the batches were '
'rejected; however, the above mentioned complaint investigations did not '
'contain an evaluation of these Out-of-Specification Investigations within '
'the investigation summary. As a result of these investigations the firm '
'initiated Change Control TCC#19- 073-W (3/18/2019) to update the compounding '
'process to (b) (4) (Oxytocin 20 units (F008446-A-W-02-05) & Oxytocin 30 '
'units (F08544-A-W-02-04)). ')
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Firm Name: Lonza Houston, Inc
Record Date: 2020-12-10 00:00:00
Topic Probability: 0.9964690804481506
Observation:
('Physical and electronic control of material storage areas is not adequate. '
'Specifically: a) There is no separate storage area for different (Db) (4) '
'products to prevent mix-ups. Bottles of (B) (4) _ intended for the U.S. '
'market, EU market, and material derived from engineering runs are stored '
'together in the same bin within freezer (D) (4) . This bin is also used to '
'store () (4) material that has been rejected by the Quality Unit but is '
'being released to the client for non-clinical use. Of note, there are '
'differences between the U.S. and EU (b) (4) manufacturing processes. b) '
'Bottles of different status materials are stored immediately adjacent to one '
'another and primary bottle labels for the (D) (4) are not adequately '
'designed to prevent mix-ups. Master U.S. label (#02-00263 v1), Master EU '
'label (#02-00318 v1), and Master Engineering label (#02-00316 v1) are the '
'same dimensions (~2inch x 3inch), font, and colors (black text on white '
'background). There is no barcode present for direct electronic control. '
'Bottles of both accepted and rejected material are designated by a '
'“RELEASED” label that has green background and black text with identical '
'font. Freezer unit (Db) (4) in room (b) (4). which is used to store the '
'(BD) (4) and (b) (4) (b) (4) is poorly maintained and organized. During '
'inspection of the freezer on December 3, 2020, it was noted that the bottom '
'of the freezer was filled with bottles of (b) (4) . many of which were '
'overturned. The bin containing the (b) (4) was stored directly on top of the '
'bottles. There was substantial frost build-up on the © bottles at the bottom '
'of the unit and on the shelves. d) , and )in On December 3, 2020, we '
'observed materials including” bags of media, bottles of (b) (4) samples '
'located in 15mL conical tubes stored on a metal rack (marked with location '
'code (D) (4) the °C storage room Ab) (4) used for incoming materials '
'storage. The metal rack does not have locations allocated in SAP material '
'inventory management software and there is no physical control such as '
'labels to indicate the status of materials stored on the rack. Your QC '
'Project Lead stated these materials are samples under test, including '
'material acceptance and stability protocol samples, but there is no visual '
'or physical indication of this. e) On December 3. 2020 we observed freezer '
'(1D) (4) in the warehouse storage room(b) (4) to be unlocked. This freezer '
'is used to store quarantined materials and contained several quarantined '
'items at the time of inspection. Procedure USWV-16230, “Receiving and '
'Release of Materials, Supplies and Equipment for GMP Use” states “Freezers '
'and refrigerators that can be locked will be kept locked.” f) During review '
'of the SAP materials management system on December 9, 2020, we noted that '
'there were five expired batches of (D) (4) —_ (part number (1) (4) ) that '
'had not been discarded. Batches (b) (4) expired on April 30, 2020. Batches '
'(DB) (4) and (b) (4) expired on September 30, 2020. Procedure USWV-27862, '
'“Disposition of Expired and Recalled Materials from GMP Inventory” states '
'that materials should be disposed of within (b) (4) of expiration. ')
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Firm Name: Hospira Inc
Record Date: 2020-01-17 00:00:00
Topic Probability: 0.9958623647689819
Observation:
('Acceptance criteria for the sampling and testing conducted by the quality '
'control unit is not adequate to assure that batches of drug products meet '
'each appropriate specification and appropriate statistical quality control '
'criteria as a condition for their approval and release. Specifically, your '
'overall endotoxin control strategy is inadequate and does not meet the '
'requirements established in SOP-9605 (6) (4) Monitoring Program and cGMPs. '
'A. There is no direct/formal confirmation of endotoxin sample hold time '
'during the manufacture of the Nivestim™ biologic drug product, including but '
'not limited to bulk samples from lot 01320DD, during compounding (BPR — '
'Compounding (b) (4) ) and unit samples from vial filling (BPR — Filling (b) '
'(4) operations, ensuring conformance to time limitations established during '
'the (b) (4) validation (PQR0056.00-16-08). B. The (b) (4) systems '
'supporting the CPM (CARPUJECT™) componentry workflow fail to achieve your '
'targeted (b) (4) reduction of endotoxin. The performance qualifications '
'report minimum endotoxin log reductions o an © @olass cartridge, '
'PQR0254.00-19-02 (b)(4)il PQR0254.00-19-02 (BY (4), 2.9 (plunger/rubber '
'component, PQRO130.20-19-07) and 1.8 ™I cap, PQRO130.20-19-06). The routine '
'(b) (4) monitoring program for componentry (SOP-96954 Sampling of '
'Manufacturing and Packaging Components), in absence of (b) (A) eduction in '
'endotoxin, does not employ a statistically valid/acceptable sampling plan. '
'For example (6) (4) glass cartridges (SOP-96954) will be assessed for '
'endotoxin from" (6) (4) batch which routinely exceeds (b) (4) units (6) (4) '
'? (b) (4) ). C. The Morphine Sulfate endotoxin specifications for '
'componentry (SOP-96054), raw materials/excipient (6)(4) ) and drug substance '
'(b) (4) do not ensure the finished drug product will meet specification (b) '
'(4) , If the drug substance, raw materials and componentry approach the '
'specification limits for endotoxin, the combined endotoxin load will exceed '
'the drug product specification. An endotoxin value in excess of the drug '
'product specification may not be detected through finished drug product '
'testing due to the very limited/inadequate sampling plan (e.g () (4) out of '
'approximately (b) (4) units for drug product, Contro (b) (4) ; (b) (4) ) D. '
'The endotoxin control strategy does not include an evaluation (e.g. (b) (4) '
'an (Db) (4) ) of the effect of hold time on the ability to detect endotoxin '
'in all applicable sterile drug products (in-process / bulk and finished). '
'Further, you have not demonstrated your ability to detect endotoxin over '
'your specified sample storage time and conditions in complex '
'formulations/matrices including but not limited to solubilization and/or '
'stabilization agents. ')
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===============================================================================
TOPIC NUMBER 8
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Firm Name: Roger Williams Medical Center
Record Date: 2019-08-14 00:00:00
Topic Probability: 0.995243489742279
Observation:
('You did not make adequate product evaluation and take remedial action where '
'actionable microbial contamination was found to be present in an area '
'adjacent to the ISO 5 classified aseptic processing area during aseptic '
'production. Specifically, you failed to present any documentation that the '
'pharmacy has adequately investigated or taken remedial action to control '
'objectionable organisms found in the ISO 7 Clean rooms. A. Routine '
'environmental monitoring done during production on 5/13/2019, resulted in an '
'airborne viable recovery of 2 CFU/m? of “Inpex (mold)” in the Chemo Room. '
'You received the May 2019 environmental monitoring report on 5/21/2019 and '
'you did not respond to the excursion until a (2)@5) of the Chemo Room was '
'performed on 5/24/2019. You continued to produce in the ISO 5 hoods from '
'5/21/2019 to 5/23/2019 before performing|(*) |) of the Chemo Room. For '
'example, you produced the chemotherapy treatments Carboplatin 623 MG in NS '
'250 MLS and Irmotecan 300 MG IV D5W500 on 5/21/2019 and Oxaliplatin 160 MG '
'in DSW 250 MLS on 5/22/2019. You did not investigate the root cause of the '
'excursion and assess the potential impact on drug products produced during '
'that period. B. Routine environmental monitoring done during production on '
'7/23/2019, resulted in an airborne viable recovery of 3 CFU/m’ of “Irpex '
'(mold)” fungal growth in the Center of the Chemo Room. During the '
'environmental monitoring you produced the drug Palonosetron 25MG/S5ML IV. '
'You received the July 2019 environmental monitoring report on 07/30/2019 and '
'you failed to investigate the root cause of the microbial contamination, '
'implement corrective actions, or assess the potential impact on drug '
'products produced during that period. C. Routine environmental monitoring '
'done on 8/08/2018, resulted in an airborne viable recovery of 1 CFU/m? of '
'“Aspergillus fumigatus (mold)” in the center of the Chemo Room and a surface '
'viable recovery of 2 CFU/25cm* of gram-negative rod bacteria '
'“Methylobacterium (bact, GNR)” in the wash sink counter of the Ante Room. '
'You received the environmental monitoring report on 8/15/2018 and the '
'next/(®)) 5) of the Chemo Room was performed 9 days later on 8/24/2018. You '
'failed to investigate the root cause of the microbial contamination and '
'implement corrective actions. In addition, you failed to present any '
'assurance objectionable organisms present in the ISO 7 Ante Room are not '
'transferred to the (4) ISO 7 Chemo Room from personnel movement between the '
'two rooms. ')
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Firm Name: John L. McClellan Memorial Veterans Hospital
Record Date: 2020-01-23 00:00:00
Topic Probability: 0.9942987561225891
Observation:
('he facility design of your cleanroom does not have a suitable construction '
'to facilitate cleaning, maintenance, and proper operations. Specifically, '
'A. Your firm ground floor inpatient pharmacy was observed to have two (2) '
'wooden doors: ¢ Wooden door that separates the anteroom from the general '
'pharmacy area; and a observations, and dd‘not représent ‘a final Agericy '
'determination régardiig your comphance. If you have an objection regarding '
'an observation, or have implemented, or plan to implement, corrective action '
'in response to an observation, you may discuss the objection or action with '
'the FDA representative(s) during the inspection or submit this information '
'to FDA at the address above. If you have any questions, please contact FDA '
'at the phone number and address above. According to your most recent '
'certification report, dated 11 November 2019, this compounding area is a '
'segregated compounding area (SCA) and contains (b) (4), LAFH (1SO-5 '
"Classified) in an unclassified area. Your firm's Chief of Pharmacy stated "
'STAT Gammediate use) for low-nsk Compounded Sterile Product (CSP) orders are '
'prepared in the LAFHs ([SO-5 Classified) of this area as a contingency '
'compounding area. This area was converted to a SCA in September '
'2019. B. Your firm utilizes(b) (4 Refrigerators to store drug '
'products, located in your “(b) (4) Mobile Unit Hazardous and Non- azardous '
'(ISO-7 Classified) Areas. According to the Service Manual provided by your '
'firm’s HVAC Supervisor for Engineering, preventative maintenance and routine '
'cleanings are to be performed on this equipment. For example, but are not '
'mae to os condenser grill is to be cleaned (6)(4) the high and low '
'temperature alarms are to be tested (B (4 b) ( ‘3 addition, a condensation '
'evaporation water tray i is eat on the backside of the refrigerators, which '
'1 is Pooling of water may occur if the (BYP is not working properly (i.e. { '
'alarms are to be tested However, according to your firm’s Chief '
'of Pharmacy, preventative maintenance has not been performed since September '
'2018. ')
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Firm Name: John L. McClellan Memorial Veterans Hospital
Record Date: 2020-01-23 00:00:00
Topic Probability: 0.9932112693786621
Observation:
('& 8): the condensation unit or water evaporation tray of the refrigerators '
'located in the [SO-7 Classified areas (Please refer to OBSERVATION 4, 7, & '
'8); inadequate cleaning practices (Please refer to OBSERVATIONS 1, 3, 6); '
'non-sterile gowning, and/or exposed skin (Please refer to OBSERVATION 5). In '
'addition, your firm’s inpatient pharmacy supervisor stated (6)(@)) cleanings '
'are routinely scheduled to occur prior to EM sampling. Your firm continued '
'aseptic operations in this room from 18 September 2019 — present, with the '
'exception of the following closures: « 15 —30 October 2019 ¢ 04-18 December '
'2019 observations, and do not represent a tinal Agency determination '
'regarding your compliance. lt you have an objection regarding an '
'observation, or have implemented, or plan to implement, corrective action in '
'response to an observation, you may discuss the objection or action with the '
'FDA representative(s) during the inspection or submit this information to '
'FDA at the address above. If you have any questions, please contact FDA at '
'the phone number and address above. fu) Count 07/08/2019 Trailer- Hazard '
'Room corner — between BSCs) 09/18/2019 Trailer-?*: Hazard Room Gram-positive '
'rods; (corner — between BSCs) Micrococcus: Staphylococcus Colagulase (-); '
'and Other Fungi 09/18/2019 Trailer™® Hazard AnteRoom Gram-positive rods; '
'(Shelf) Micrococcus; Staphylococcus 09/30/2019 Trailer-~~ Hazard Room Near '
'Gram-negative rods; Staphylococcus Colagulase (- ); and Other 10/08/2019 '
'Trailer}: Hazard Room Near Gram-negative rods; ae 11/26/2019 aes Hazard '
'Room Near Other Fungi According to your firm’s 6-month prescription log, '
'your firm compounded approximately (6) (A)units of sterile drug products in '
'your firm’s Hazardous Room. ')
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